The objectives of the proposed research are 1) to determine and quantitate the factors influencing FSH and LH secretion in normal men, principally by utilizing synthetic FSH/LH-releasing hormone (gonadotropin-releasing hormone, GnRH; and 2) to apply what is learned about FSH and LH secretion in normal men to the evaluation, and possible treatment, of abnormalities at all levels of the hypothalamic-pituitary- testicular axis. The FSH and LH responses to graded doses of GnRH have already been determined in normal young men. The effect of the male senescence on the FSH and LH responses to GnRH is currently being investigated, and the results will be correlated with serum testosterone levels and semen analyses. Next, the effects of modifying the serum levels of testosterone, estradiol, and other steroids, acutely and chronically, on the responses to GnRH will be determined in normal subjects and in patients with primary testicular damage. The serum FSH and LH responses to the acute administration of GnRH should help to determine whether or not these responses are impaired in patients with pituitary disease prior to impairment of testosterone secretion and/or spermatogenesis, and whether they are supranormal in patients with primary testicular disease before basal serum FSH and LH levels are elevated. Chronic parenteral administration of GnRH to patients with idiopathic hypogonadotropic-hypogonadism, as well as to normal control subjects, and determination of the FSH, LH, testosterone, and spermatogenic responses, should answer fundamental questions about this (these) abnormality(ies), regardless of whether or not normal testicular function is restored.